期刊
CELL STEM CELL
卷 4, 期 2, 页码 129-140出版社
CELL PRESS
DOI: 10.1016/j.stem.2008.11.015
关键词
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资金
- Leikaemia Research Fund (UK)
- Cancer Research UK [C147/A6058]
- National Cancer Institute, Department of Health and Human Services [T32 CA09151]
- American Cancer Society
- Children's Health Initiative of the Packard Foundation [CA55029, CA116606]
- Leukemia and Lymphoma Society
The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional subprogram more akin to that of embryonic stem cells (ESCs) than to that of adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3, and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when coexpressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia-initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor-prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells (CSCs) to prognosis in human cancer.
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